Judith Simcox, PhD
Position title: Assistant Professor, Biochemistry
371b Biochemistry Labs
433 Babcock Dr
The research objectives of my laboratory are to investigate the mechanisms that promote energy expenditure during adaptive thermogenesis. Our work focuses on identifying transcriptional regulators of hepatic lipid processing that fuel thermogenesis and discovering lipid signaling pathways that orchestrate multi-organ communication during cold stress.
The Simcox laboratory focuses on two unanswered questions:
1) How are liver-produced lipids taken up & metabolized in brown adipocytes?
Brown adipocytes increase uptake of circulating lipids 12-fold during cold exposure, but the contribution of the various lipid species to thermogenesis remains elusive. We will use heavy isotope and fluorescently labeled lipids to identify lipid importers, assess metabolic pathways of uptake, and characterize the functional importance of various lipid species in isolated brown adipocytes.
2) How is hepatic lipid processing regulated in cold exposure?
Hepatic lipid processing is required for mice to maintain their body temperature in response to cold exposure. In untargeted lipidomic analysis we identified several hundred hepatic lipids that are altered in cold exposure and correlate with changes in circulating lipids. We will functionally characterize the role of these lipids in cold exposure and identify the transcriptional programs that regulate their production and clearance.
- Simcox JA, Mitchell CM, Gao Y, Just SF, Cooksey B, Cox J, Ajioka R, Jones D, Lee S, King D, Huang J, and DA McClain. Dietary iron controls circadian rhythm of hepatic glucose metabolism through heme synthesis. 2014. 64(4):1108-19. PMCID: PMC4375081
- Simcox JA, DA McClain. Iron and diabetes risk. 2013. Cell Metabolism. 17(3):329-41. PMCID: PMC3648340
- Simcox JA, Geoghegan G, Machek JA, Bensard CL, Pasquali M, Miao R, Lee S, Jiang L, Huck I, Kershaw EE, Donato AJ, Apte U, Long N, Rutter J, Schreiber R, Zechner R, Cox J, and CJ Villanueva. Global analysis of plasma lipids identifies liver-derived acyl-carnitines as a fuel source for brown fat thermogenesis. 2017. Cell Metabolism. 5;26(3):509-522.e6. *Featured as Cover Story PMCID: PMC6531814
- Geoghegan G*, Simcox J*, Seldin M, Parnell T, Stubben C, Just S, Begaye L, Luis A, and CJ Villanueva. Targeted deletion of diabetes risk gene Tcf7l2 in adipocytes promotes adipocyte hypertrophy and impaired glucose metabolism. 2018. Molecular Metabolism. pii: S2212-8778(18)31029-9. doi: 10.1016/j.molmet.2019.03.003. *indicates co-first authorship. PMCID: PMC5658052